JP6002763B2 - グラム陰性細菌の外膜小胞を、洗浄剤を含まずに生産するためのプロセス - Google Patents
グラム陰性細菌の外膜小胞を、洗浄剤を含まずに生産するためのプロセス Download PDFInfo
- Publication number
- JP6002763B2 JP6002763B2 JP2014518850A JP2014518850A JP6002763B2 JP 6002763 B2 JP6002763 B2 JP 6002763B2 JP 2014518850 A JP2014518850 A JP 2014518850A JP 2014518850 A JP2014518850 A JP 2014518850A JP 6002763 B2 JP6002763 B2 JP 6002763B2
- Authority
- JP
- Japan
- Prior art keywords
- omv
- bacteria
- process according
- gram
- medium
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000000034 method Methods 0.000 title claims description 89
- 241000894006 Bacteria Species 0.000 title claims description 77
- 230000008569 process Effects 0.000 title claims description 71
- 239000012528 membrane Substances 0.000 title claims description 25
- 239000003599 detergent Substances 0.000 title claims description 17
- 229960005486 vaccine Drugs 0.000 claims description 70
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical group OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 41
- 239000002184 metal Substances 0.000 claims description 40
- 239000002738 chelating agent Substances 0.000 claims description 39
- 239000000427 antigen Substances 0.000 claims description 33
- 102000036639 antigens Human genes 0.000 claims description 33
- 108091007433 antigens Proteins 0.000 claims description 33
- 108090000623 proteins and genes Proteins 0.000 claims description 29
- 239000002671 adjuvant Substances 0.000 claims description 26
- 231100000419 toxicity Toxicity 0.000 claims description 23
- 230000001988 toxicity Effects 0.000 claims description 23
- 238000004519 manufacturing process Methods 0.000 claims description 22
- 241000588650 Neisseria meningitidis Species 0.000 claims description 21
- 230000001580 bacterial effect Effects 0.000 claims description 19
- 230000000694 effects Effects 0.000 claims description 17
- 230000002829 reductive effect Effects 0.000 claims description 16
- 230000003698 anagen phase Effects 0.000 claims description 13
- GZQKNULLWNGMCW-PWQABINMSA-N lipid A (E. coli) Chemical compound O1[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@@H](NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@@H]1OC[C@@H]1[C@@H](O)[C@H](OC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](OP(O)(O)=O)O1 GZQKNULLWNGMCW-PWQABINMSA-N 0.000 claims description 12
- 239000011148 porous material Substances 0.000 claims description 10
- 101150093941 PORA gene Proteins 0.000 claims description 8
- 241000894007 species Species 0.000 claims description 8
- 238000012239 gene modification Methods 0.000 claims description 6
- 230000005017 genetic modification Effects 0.000 claims description 6
- 235000013617 genetically modified food Nutrition 0.000 claims description 6
- 230000004048 modification Effects 0.000 claims description 6
- 238000012986 modification Methods 0.000 claims description 6
- 230000035772 mutation Effects 0.000 claims description 6
- 238000012258 culturing Methods 0.000 claims description 5
- 101150024840 rmpM gene Proteins 0.000 claims description 5
- 230000001954 sterilising effect Effects 0.000 claims description 5
- 238000004659 sterilization and disinfection Methods 0.000 claims description 5
- 241000588807 Bordetella Species 0.000 claims description 4
- 241000588653 Neisseria Species 0.000 claims description 4
- 239000000284 extract Substances 0.000 claims description 4
- 101150031507 porB gene Proteins 0.000 claims description 4
- 238000011084 recovery Methods 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 101150070011 lpxK gene Proteins 0.000 claims description 3
- 101150047779 ompB gene Proteins 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 101100407670 Pseudoalteromonas haloplanktis pepQ gene Proteins 0.000 claims description 2
- 230000001851 biosynthetic effect Effects 0.000 claims description 2
- 101150083361 lpxE gene Proteins 0.000 claims description 2
- 101150031431 opa gene Proteins 0.000 claims description 2
- 101150050459 pagL gene Proteins 0.000 claims description 2
- 241000588832 Bordetella pertussis Species 0.000 claims 1
- 239000003990 capacitor Substances 0.000 claims 1
- 230000009920 chelation Effects 0.000 claims 1
- 239000002158 endotoxin Substances 0.000 description 44
- 229920006008 lipopolysaccharide Polymers 0.000 description 41
- 239000002609 medium Substances 0.000 description 41
- 230000012010 growth Effects 0.000 description 17
- 239000001963 growth medium Substances 0.000 description 15
- 230000028993 immune response Effects 0.000 description 14
- 239000000047 product Substances 0.000 description 13
- 239000000872 buffer Substances 0.000 description 12
- 239000003814 drug Substances 0.000 description 12
- 238000000605 extraction Methods 0.000 description 11
- 230000005847 immunogenicity Effects 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 10
- 108020004414 DNA Proteins 0.000 description 9
- 102000053602 DNA Human genes 0.000 description 9
- 201000009906 Meningitis Diseases 0.000 description 9
- 238000005119 centrifugation Methods 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 8
- 238000011026 diafiltration Methods 0.000 description 8
- 208000037941 meningococcal disease Diseases 0.000 description 8
- 239000008194 pharmaceutical composition Substances 0.000 description 8
- 125000002252 acyl group Chemical group 0.000 description 7
- -1 glucosamine disaccharide Chemical class 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 150000001413 amino acids Chemical class 0.000 description 6
- 230000000844 anti-bacterial effect Effects 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 150000004676 glycans Chemical class 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 229920001282 polysaccharide Polymers 0.000 description 6
- 239000005017 polysaccharide Substances 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 230000005526 G1 to G0 transition Effects 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 241000282414 Homo sapiens Species 0.000 description 5
- 208000034762 Meningococcal Infections Diseases 0.000 description 5
- 241000588677 Neisseria meningitidis serogroup B Species 0.000 description 5
- 108010034546 Serratia marcescens nuclease Proteins 0.000 description 5
- 125000003275 alpha amino acid group Chemical group 0.000 description 5
- 239000002518 antifoaming agent Substances 0.000 description 5
- 239000012459 cleaning agent Substances 0.000 description 5
- 238000012217 deletion Methods 0.000 description 5
- 230000037430 deletion Effects 0.000 description 5
- 239000003937 drug carrier Substances 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 235000015097 nutrients Nutrition 0.000 description 5
- 238000011146 sterile filtration Methods 0.000 description 5
- 238000002255 vaccination Methods 0.000 description 5
- 101710186862 Factor H binding protein Proteins 0.000 description 4
- 101710116435 Outer membrane protein Proteins 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 230000002238 attenuated effect Effects 0.000 description 4
- 238000012512 characterization method Methods 0.000 description 4
- 230000009089 cytolysis Effects 0.000 description 4
- 210000004443 dendritic cell Anatomy 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 238000002649 immunization Methods 0.000 description 4
- 230000001939 inductive effect Effects 0.000 description 4
- 101150011311 lpxL gene Proteins 0.000 description 4
- 238000001471 micro-filtration Methods 0.000 description 4
- 244000005700 microbiome Species 0.000 description 4
- 150000007523 nucleic acids Chemical class 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 150000003904 phospholipids Chemical class 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000000108 ultra-filtration Methods 0.000 description 4
- 239000002028 Biomass Substances 0.000 description 3
- 102000014914 Carrier Proteins Human genes 0.000 description 3
- 108010078791 Carrier Proteins Proteins 0.000 description 3
- 241000606161 Chlamydia Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 238000004220 aggregation Methods 0.000 description 3
- 230000002776 aggregation Effects 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 3
- 238000005352 clarification Methods 0.000 description 3
- 229940001442 combination vaccine Drugs 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000002523 gelfiltration Methods 0.000 description 3
- 229960002442 glucosamine Drugs 0.000 description 3
- 244000000058 gram-negative pathogen Species 0.000 description 3
- 230000003053 immunization Effects 0.000 description 3
- 230000003308 immunostimulating effect Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 229940124731 meningococcal vaccine Drugs 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 230000036284 oxygen consumption Effects 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 238000005199 ultracentrifugation Methods 0.000 description 3
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 2
- AZXKALLRCOCGBV-UHFFFAOYSA-N 1-phenyl-2-(propan-2-ylamino)hexan-1-one Chemical compound CCCCC(NC(C)C)C(=O)C1=CC=CC=C1 AZXKALLRCOCGBV-UHFFFAOYSA-N 0.000 description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 101710154607 Azurocidin Proteins 0.000 description 2
- 102100030009 Azurocidin Human genes 0.000 description 2
- FTEDXVNDVHYDQW-UHFFFAOYSA-N BAPTA Chemical compound OC(=O)CN(CC(O)=O)C1=CC=CC=C1OCCOC1=CC=CC=C1N(CC(O)=O)CC(O)=O FTEDXVNDVHYDQW-UHFFFAOYSA-N 0.000 description 2
- 101100451792 Bacillus subtilis (strain 168) htrB gene Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 241000991587 Enterovirus C Species 0.000 description 2
- 101100221862 Gibberella fujikuroi cps gene Proteins 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 241000606768 Haemophilus influenzae Species 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 2
- 108700018753 Neisseria porin Proteins 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 201000005702 Pertussis Diseases 0.000 description 2
- 108010081690 Pertussis Toxin Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- 101100021843 Shigella flexneri lpxM1 gene Proteins 0.000 description 2
- 101100021844 Shigella flexneri lpxM2 gene Proteins 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 230000005875 antibody response Effects 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 244000052616 bacterial pathogen Species 0.000 description 2
- 239000012620 biological material Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 208000002352 blister Diseases 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000000139 costimulatory effect Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 229960003983 diphtheria toxoid Drugs 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 238000011143 downstream manufacturing Methods 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 229940047650 haemophilus influenzae Drugs 0.000 description 2
- 239000012510 hollow fiber Substances 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000008297 liquid dosage form Substances 0.000 description 2
- 101150060640 lpxM gene Proteins 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 101150019075 neuA gene Proteins 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 239000002357 osmotic agent Substances 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 229960003330 pentetic acid Drugs 0.000 description 2
- 108010021711 pertactin Proteins 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000005180 public health Effects 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 230000003362 replicative effect Effects 0.000 description 2
- 229920002477 rna polymer Polymers 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000012536 storage buffer Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 229960000814 tetanus toxoid Drugs 0.000 description 2
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- JRMAQQQTXDJDNC-UHFFFAOYSA-M 2-ethoxy-2-oxoacetate Chemical compound CCOC(=O)C([O-])=O JRMAQQQTXDJDNC-UHFFFAOYSA-M 0.000 description 1
- 241000606750 Actinobacillus Species 0.000 description 1
- 229910017119 AlPO Inorganic materials 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 244000105975 Antidesma platyphyllum Species 0.000 description 1
- 101150013553 CD40 gene Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 101100329455 Cereibacter sphaeroides (strain ATCC 17023 / DSM 158 / JCM 6121 / CCUG 31486 / LMG 2827 / NBRC 12203 / NCIMB 8253 / ATH 2.4.1.) crtC gene Proteins 0.000 description 1
- 101100245206 Dictyostelium discoideum psmC4 gene Proteins 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000606790 Haemophilus Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 102000003814 Interleukin-10 Human genes 0.000 description 1
- 102000013462 Interleukin-12 Human genes 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 101100368149 Mus musculus Sync gene Proteins 0.000 description 1
- 241000588652 Neisseria gonorrhoeae Species 0.000 description 1
- 241000588649 Neisseria lactamica Species 0.000 description 1
- 241001174901 Neisseria meningitidis alpha275 Species 0.000 description 1
- 241000921898 Neisseria meningitidis serogroup A Species 0.000 description 1
- 101100203230 Neisseria meningitidis serogroup B (strain MC58) siaA gene Proteins 0.000 description 1
- 101100259999 Neisseria meningitidis serogroup B (strain MC58) tbp1 gene Proteins 0.000 description 1
- 241000947238 Neisseria meningitidis serogroup C Species 0.000 description 1
- 241001573069 Neisseria meningitidis serogroup Y Species 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000606860 Pasteurella Species 0.000 description 1
- 241000606856 Pasteurella multocida Species 0.000 description 1
- 208000035109 Pneumococcal Infections Diseases 0.000 description 1
- 208000000474 Poliomyelitis Diseases 0.000 description 1
- 229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 101710194807 Protective antigen Proteins 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 206010043376 Tetanus Diseases 0.000 description 1
- 108010092220 Tetraacyldisaccharide 4'-kinase Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
- 101100226309 Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961) exbB1 gene Proteins 0.000 description 1
- 101100119307 Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961) exbD1 gene Proteins 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000005273 aeration Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000006472 autoimmune response Effects 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 230000008436 biogenesis Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 238000012769 bulk production Methods 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000010960 commercial process Methods 0.000 description 1
- 238000010835 comparative analysis Methods 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 101150019098 cps gene Proteins 0.000 description 1
- 101150059761 ctrA gene Proteins 0.000 description 1
- 101150056963 ctrB gene Proteins 0.000 description 1
- 101150117300 ctrC gene Proteins 0.000 description 1
- 101150055828 ctrD gene Proteins 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 230000000779 depleting effect Effects 0.000 description 1
- 238000011118 depth filtration Methods 0.000 description 1
- 230000001687 destabilization Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 206010013023 diphtheria Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 101150080665 exbB gene Proteins 0.000 description 1
- 101150074952 exbD gene Proteins 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000005243 fluidization Methods 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 101150002054 galE gene Proteins 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N glucosamine group Chemical group OC1[C@H](N)[C@@H](O)[C@H](O)[C@H](O1)CO MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 235000009424 haa Nutrition 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 244000052637 human pathogen Species 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229920000831 ionic polymer Polymers 0.000 description 1
- 101150057984 isdB gene Proteins 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 125000000400 lauroyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000012768 mass vaccination Methods 0.000 description 1
- 238000002887 multiple sequence alignment Methods 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 239000003471 mutagenic agent Substances 0.000 description 1
- 231100000707 mutagenic chemical Toxicity 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- MGFYIUFZLHCRTH-UHFFFAOYSA-N nitrilotriacetic acid Chemical compound OC(=O)CN(CC(O)=O)CC(O)=O MGFYIUFZLHCRTH-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 238000000424 optical density measurement Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 description 1
- 229940051027 pasteurella multocida Drugs 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 238000009521 phase II clinical trial Methods 0.000 description 1
- 101150028857 phoP gene Proteins 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000002516 postimmunization Effects 0.000 description 1
- 230000001124 posttranscriptional effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 238000011165 process development Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 101150054232 pyrG gene Proteins 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000009781 safety test method Methods 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 238000011218 seed culture Methods 0.000 description 1
- 238000012807 shake-flask culturing Methods 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 101150057501 synA gene Proteins 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 101150032923 tbpA gene Proteins 0.000 description 1
- 101150095556 tbpB gene Proteins 0.000 description 1
- 101150084216 thiB gene Proteins 0.000 description 1
- 229960004906 thiomersal Drugs 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- STCOOQWBFONSKY-UHFFFAOYSA-N tributyl phosphate Chemical compound CCCCOP(=O)(OCCCC)OCCCC STCOOQWBFONSKY-UHFFFAOYSA-N 0.000 description 1
- 239000011800 void material Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/095—Neisseria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/04—Chelating agents
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/52—Bacterial cells; Fungal cells; Protozoal cells
- A61K2039/522—Bacterial cells; Fungal cells; Protozoal cells avirulent or attenuated
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/52—Bacterial cells; Fungal cells; Protozoal cells
- A61K2039/523—Bacterial cells; Fungal cells; Protozoal cells expressing foreign proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55505—Inorganic adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/70—Multivalent vaccine
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2500/00—Specific components of cell culture medium
- C12N2500/05—Inorganic components
- C12N2500/10—Metals; Metal chelators
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2500/00—Specific components of cell culture medium
- C12N2500/60—Buffer, e.g. pH regulation, osmotic pressure
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Toxicology (AREA)
- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Detergent Compositions (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201161505221P | 2011-07-07 | 2011-07-07 | |
EP11173085.9 | 2011-07-07 | ||
EP11173085 | 2011-07-07 | ||
US61/505,221 | 2011-07-07 | ||
PCT/NL2012/050478 WO2013006055A1 (en) | 2011-07-07 | 2012-07-05 | A process for detergent-free production of outer membrane vesicles |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2014520801A JP2014520801A (ja) | 2014-08-25 |
JP2014520801A5 JP2014520801A5 (pt) | 2015-08-06 |
JP6002763B2 true JP6002763B2 (ja) | 2016-10-05 |
Family
ID=47437254
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014518850A Active JP6002763B2 (ja) | 2011-07-07 | 2012-07-05 | グラム陰性細菌の外膜小胞を、洗浄剤を含まずに生産するためのプロセス |
Country Status (19)
Country | Link |
---|---|
US (2) | US9272006B2 (pt) |
EP (1) | EP2729167B1 (pt) |
JP (1) | JP6002763B2 (pt) |
CN (1) | CN103687612B (pt) |
AU (1) | AU2012278407B2 (pt) |
CA (1) | CA2840096C (pt) |
DK (1) | DK2729167T3 (pt) |
ES (1) | ES2670669T3 (pt) |
HR (1) | HRP20180890T1 (pt) |
HU (1) | HUE037969T2 (pt) |
IL (1) | IL230326B (pt) |
LT (1) | LT2729167T (pt) |
PL (1) | PL2729167T3 (pt) |
PT (1) | PT2729167T (pt) |
RS (1) | RS57267B1 (pt) |
RU (1) | RU2607021C2 (pt) |
SI (1) | SI2729167T1 (pt) |
TR (1) | TR201808206T4 (pt) |
WO (1) | WO2013006055A1 (pt) |
Families Citing this family (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2790167C (en) | 2010-03-30 | 2021-02-09 | Children's Hospital & Research Center Oakland | Factor h binding proteins (fhbp) with altered properties and methods of use thereof |
CA2840096C (en) * | 2011-07-07 | 2021-07-06 | Bas VAN DE WATERBEEMD | A process for detergent-free production of outer membrane vesicles of a gram-negative bacterium |
US10279026B2 (en) * | 2012-04-26 | 2019-05-07 | Glaxosmithkline Biologicals Sa | Antigens and antigen combinations |
SG11201600334SA (en) | 2013-08-02 | 2016-02-26 | Children S Hospital & Res Ct Oakland | Non-naturally occurring factor h binding proteins (fhbp) and methods of use thereof |
EP4074726A3 (en) | 2014-07-23 | 2022-11-23 | Children's Hospital & Research Center at Oakland | Factor h binding protein variants and methods of use thereof |
KR101715366B1 (ko) * | 2014-09-04 | 2017-03-14 | 한국과학기술연구원 | 지질의 탈인산화용 조성물, 키트, 및 이를 이용한 탈인산화된 지질을 생산하는 방법 |
AU2015352404A1 (en) * | 2014-11-28 | 2017-05-18 | Janssen Vaccines & Prevention B.V. | Meningitis B vaccine |
WO2016193370A1 (en) | 2015-06-02 | 2016-12-08 | De Staat Der Nederlanden, Vert. Door De Minister Van Vws, Ministerie Van Volksgezondheid, Welzijn En Sport | Surface display of antigens on gram-negative outer membrane vesicles |
AU2017211975B2 (en) * | 2016-01-28 | 2021-03-25 | Intravacc B.V. | Modified tetra-acylated neisserial LPS |
CN109071587B (zh) | 2016-01-28 | 2022-11-01 | 由卫生福利和体育大臣代表的荷兰王国 | 经修饰的六酰化奈瑟球菌lps |
EP3544625A2 (en) | 2016-11-25 | 2019-10-02 | GlaxoSmithKline Biologicals S.A. | Immunogenic conjugates and use thereof |
JP7311227B2 (ja) | 2017-03-13 | 2023-07-19 | イントラヴァック ビー.ブイ. | 低下した反応源性を有するlpsを含むボルデテラワクチン |
EP3720945A1 (en) * | 2017-12-04 | 2020-10-14 | De Staat der Nederlanden, vert. door de minister van VWS, Ministerie van Volksgezondheid, Welzjin en Sport | An improved process for producing outer membrane vesicles |
TW202045192A (zh) * | 2019-02-22 | 2020-12-16 | 美商艾弗洛生物科技股份有限公司 | 細菌膜製劑 |
JP2023525294A (ja) | 2020-05-08 | 2023-06-15 | イントラヴァック ベスローテン フェノーツハップ | クリックomv |
EP4208472A1 (en) | 2020-09-04 | 2023-07-12 | Intravacc B.V. | Ompa mutations enhance omv production in bordetella pertussis |
CN115216478B (zh) * | 2022-06-01 | 2024-03-26 | 华南农业大学 | 一种禽多杀性巴氏杆菌内毒素减毒灭活疫苗菌株的构建方法及应用 |
CN115976088B (zh) * | 2022-07-21 | 2023-09-19 | 深圳蓝晶生物科技有限公司 | 低内毒素含量的罗氏真养菌及其应用 |
CN118240723A (zh) * | 2024-05-29 | 2024-06-25 | 上海羽冠生物技术有限公司 | 一种通过发酵产生细菌外膜囊泡的方法 |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5997881A (en) | 1995-11-22 | 1999-12-07 | University Of Maryland, Baltimore | Method of making non-pyrogenic lipopolysaccharide or A |
US6558677B2 (en) * | 1996-10-15 | 2003-05-06 | Wendell D. Zollinger | Vaccine against gram negative bacteria |
EP1127137B2 (en) | 1998-11-03 | 2013-12-25 | De Staat Der Nederlanden Vertegenwoordigd Door De Minister Van Welzijn, Volksgezondheid En Cultuur | Lps with reduced toxicity from genetically modified gram negative bacteria |
GB0103170D0 (en) * | 2001-02-08 | 2001-03-28 | Smithkline Beecham Biolog | Vaccine composition |
EP2255826B1 (en) * | 2002-08-02 | 2016-04-13 | GlaxoSmithKline Biologicals S.A. | Neisserial vaccine compositions comprising a combination of antigens |
GB0220194D0 (en) * | 2002-08-30 | 2002-10-09 | Chiron Spa | Improved vesicles |
PT1748791E (pt) | 2004-05-11 | 2010-07-15 | Staat Der Nederlanden Vert Doo | Los de neisseria meningitidis lgtb utlizados como adjuvantes |
RU2432962C2 (ru) * | 2005-01-27 | 2011-11-10 | Чилдрен'З Хоспитал Энд Рисерч Сентер Эт Окленд | Вакцины с использованием везикул на основе gna 1870 широкого спектра действия для профилактики заболеваний, вызываемых neisseria meningitidis |
CA2840096C (en) * | 2011-07-07 | 2021-07-06 | Bas VAN DE WATERBEEMD | A process for detergent-free production of outer membrane vesicles of a gram-negative bacterium |
-
2012
- 2012-07-05 CA CA2840096A patent/CA2840096C/en active Active
- 2012-07-05 DK DK12740235.2T patent/DK2729167T3/en active
- 2012-07-05 EP EP12740235.2A patent/EP2729167B1/en active Active
- 2012-07-05 US US14/131,279 patent/US9272006B2/en active Active
- 2012-07-05 SI SI201231292T patent/SI2729167T1/sl unknown
- 2012-07-05 ES ES12740235.2T patent/ES2670669T3/es active Active
- 2012-07-05 WO PCT/NL2012/050478 patent/WO2013006055A1/en active Application Filing
- 2012-07-05 RU RU2014104241A patent/RU2607021C2/ru active
- 2012-07-05 TR TR2018/08206T patent/TR201808206T4/tr unknown
- 2012-07-05 AU AU2012278407A patent/AU2012278407B2/en active Active
- 2012-07-05 LT LTEP12740235.2T patent/LT2729167T/lt unknown
- 2012-07-05 PT PT127402352T patent/PT2729167T/pt unknown
- 2012-07-05 CN CN201280033688.2A patent/CN103687612B/zh active Active
- 2012-07-05 HU HUE12740235A patent/HUE037969T2/hu unknown
- 2012-07-05 JP JP2014518850A patent/JP6002763B2/ja active Active
- 2012-07-05 RS RS20180634A patent/RS57267B1/sr unknown
- 2012-07-05 PL PL12740235T patent/PL2729167T3/pl unknown
-
2014
- 2014-01-05 IL IL230326A patent/IL230326B/en active IP Right Grant
-
2016
- 2016-02-17 US US15/045,424 patent/US9707286B2/en active Active
-
2018
- 2018-06-06 HR HRP20180890TT patent/HRP20180890T1/hr unknown
Also Published As
Publication number | Publication date |
---|---|
SI2729167T1 (sl) | 2018-09-28 |
US9707286B2 (en) | 2017-07-18 |
WO2013006055A8 (en) | 2013-08-15 |
ES2670669T3 (es) | 2018-05-31 |
US9272006B2 (en) | 2016-03-01 |
EP2729167A1 (en) | 2014-05-14 |
PT2729167T (pt) | 2018-06-20 |
US20160303214A1 (en) | 2016-10-20 |
AU2012278407B2 (en) | 2017-01-19 |
CN103687612B (zh) | 2017-12-15 |
EP2729167B1 (en) | 2018-03-14 |
HUE037969T2 (hu) | 2018-09-28 |
CN103687612A (zh) | 2014-03-26 |
LT2729167T (lt) | 2018-06-25 |
DK2729167T3 (en) | 2018-04-30 |
TR201808206T4 (tr) | 2018-07-23 |
AU2012278407A1 (en) | 2014-01-16 |
NZ618918A (en) | 2015-10-30 |
JP2014520801A (ja) | 2014-08-25 |
RU2607021C2 (ru) | 2017-01-10 |
HRP20180890T1 (hr) | 2018-09-07 |
CA2840096A1 (en) | 2013-01-10 |
IL230326B (en) | 2018-03-29 |
RS57267B1 (sr) | 2018-08-31 |
US20140147469A1 (en) | 2014-05-29 |
PL2729167T3 (pl) | 2018-08-31 |
WO2013006055A1 (en) | 2013-01-10 |
CA2840096C (en) | 2021-07-06 |
RU2014104241A (ru) | 2015-08-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6002763B2 (ja) | グラム陰性細菌の外膜小胞を、洗浄剤を含まずに生産するためのプロセス | |
ES2369852T3 (es) | Ultrafiltración y ultracentrifugación para preparar vesículas de membrana externa. | |
RU2475496C2 (ru) | МЕНИНГОКОККОВЫЕ ПОЛИПЕПТИДЫ fHBP | |
JP5465676B2 (ja) | 連鎖球菌属を培養するための発酵プロセスおよび連鎖球菌属由来の莢膜多糖(cp)を得るための精製プロセス | |
RU2325184C2 (ru) | Улучшенные везикулы наружной мембраны бактерий | |
AU2005298332B2 (en) | Immunogenic bacterial vesicles with outer membrane proteins | |
US6355253B1 (en) | Preparation and uses of LOS-depleted outer membrane proteins of gram-negative cocci | |
RU2477145C2 (ru) | Мультивалентная вакцина из нативных везикул наружной мембраны менингококков, способы ее получения и применения | |
RU2627156C2 (ru) | Высокоэффективный способ получения бактериального полисахарида, получение конъюгата на его основе и иммуногенная композиция | |
RO120819B1 (ro) | Vaccinuri dtp multivalente | |
US20110262484A1 (en) | Outer membrane vesicle prime-protein boost vaccine | |
JP2016093202A (ja) | 髄膜炎菌における増加したタンパク質発現のためのプロモータ | |
NZ618918B2 (en) | A process for detergent-free production of outer membrane vesicles of a gram-negative bacterium | |
RU2407792C1 (ru) | СПОСОБ ПОЛУЧЕНИЯ IgAl-ПРОТЕАЗЫ ИЗ КУЛЬТУРЫ NEISSERIA MENINGITIDIS СЕРОГРУППЫ А И ИММУНОГЕННЫЙ ПРЕПАРАТ НА ЕЕ ОСНОВЕ | |
TW202325338A (zh) | 氣腫疽梭菌疫苗及製備方法 | |
JP2024529055A (ja) | Clostridium chauvoeiワクチン及び作製方法 | |
WO2012153302A1 (en) | Antipyretics to enhance tolerability of vesicle-based vaccines | |
RU2005102587A (ru) | Вакцинная композиция, содержащая трансферрин-связывающий белок и hsf из грамотрицательных бактерий |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150618 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20150618 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160420 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160719 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20160720 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20160810 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20160905 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6002763 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |